1. Technical Field
The invention relates to improving water solubility of poorly water soluble and insoluble actives. More specifically, it relates to improving the aqueous solubility of a variety of materials produced for the pharmaceutical, agricultural, personal care, and similar industries.
2. Background of the Art
Many of the active compounds used in the pharmaceutical, agricultural, personal care, and similar industries require some degree of dissolution in order to carry out the function for which they are intended. Included among these are, for example, certain analgesics, such as ibuprofen; agricultural compounds, such as ketoconazole; and personal care compounds, such as salicylic acid. This dissolution may be necessary in order to enable the active compound to be useful in a selected environment. This need may create challenges where the active compound is either insoluble in the environment wherein its function is desired, or is only slightly or very slightly soluble therein. In these cases it has been found desirable or necessary to combine the active compound in some way with another material, which serves to enhance its solubility.
A variety of approaches have been pursued to modify solubility of active compounds. As used herein, solubility is defined as the concentration of solute in a saturated solution, and is therefore dependent on factors such as, for example, temperature, solvent, pH of the solution, and pressure. For pharmaceuticals in particular, the solubility of an active compound may be expressed as the number of milliliters of solvent in which one gram of solute (the active compound) will dissolve. For example, in order for a medication to be given orally, the required dose should be able to dissolve in 100-400 mL of water, which is the volume of fluid normally found in the gastrointestinal tract. Because an exact measure of solubility may be difficult to obtain for a given active, solubilities may be generically classified as falling within a given range. These ranges are defined using terms such as “slightly soluble,” “sparingly soluble,” and the like.
In order to modify solubility of various active compounds, those skilled in the art have generally taken steps such as adjusting the pH, using co-solvents, developing micellar and liposomal systems, forming microemulsions, and employing approaches including complexation, micronization, and nanoization. While each of these approaches has found useful applications, most increase the cost and/or number of steps needed to produce a given product.
For example, U.S. Pat. No. 3,784,684 discloses an oral drug delivery system employing polyethylene glycol (PEG) having a molecular weight of 600 as a component of a solvent system. U.S. Pat. No. 5,071,643 discloses a solvent system containing PEG, water, potassium hydroxide, and polyvinyl pyrrolidone (PVP). WO 95/04527 discloses a solvent system for use in gelatin capsules including PEG, propylene glycol, water, PVP, and potassium or sodium acetate. U.S. Pat. No. 4,690,823 describes a method for preparing ibuprofen-filled soft gel capsules employing ethylene oxide/propylene oxide (EO/PO) block copolymers, surfactant, and/or PEG as part of the solvent system. U.S. Pat. No. 4,859,704 describes enhancing the solubility of ibuprofen in drug formulations by using the salt form of ibuprofen. U.S. Pat. No. 4,861,797 discloses a method for making a palatable ibuprofen composition by dissolving the salt form of the active compound in a solution of water and methylcellulose. U.S. Pat. No. 4,944,949 discloses a drug delivery system employing various nonionic surfactants including PEG fatty acid esters. U.S. Pat. No. 5,141,961 discloses a solvent system using PEG, PVP, and lower alcohols. WO 2003/045357 discloses a formulation for dissolving sparingly water soluble drugs incorporating liquid PEG and derivatized methoxypolyethylene glycol (MPEG) as a surfactant. WO 0139725 describes a wound dressing and transdermal drug delivery system containing MPEG. WO 9834592 discloses a transdermal drug delivery system containing MPEG and methylcellulose for delivery of actives such as non-steroidal anti-inflammatory drugs.
While it will be seen that there are, indeed, a number of ways to enhance the solubility of actives, there are an ever-increasing number of identified actives having their own solubility limitations. Furthermore, ease, convenience and cost of the various known systems are not always optimized. Thus, there is still a need for low cost, effective means to enhance the solubility of certain active compounds in order to enable their use for an intended function.